Production of chemotactic peptides by neutrophil degradation of heparin cofactor II.
This study investigated the reaction of heparin cofactor II (HCII) with stimulated polymorphonuclear leukocytes (PMN). We have expanded upon previous studies showing that HCII can be degraded by stimulated PMN (Sie, P., Dupouy, D., Dol, F., and Boneu, B., Thromb. Res. 47, 657-664, 1987), and that chemotactic activity is produced when HCII is partially proteolyzed with purified leukocyte elastase or cathepsin G (Hoffman, M., Pratt, C.W., Brown, R.L., and Church, F.C., Blood, 73, 1682-1695, 1989). We found that HCII was proteolyzed by stimulated PMN, generating peptides with chemotactic activity. Both proteolysis and generation of chemotactic activity were inhibited by a specific leukocyte elastase inhibitor and by more general proteinase inhibitors. Leukocyte elastase activity was lost upon addition of either inhibitor. Heparin and dermatan sulfate altered the pattern of proteolysis. Our results suggest that HCII may be involved not only in functions related to thrombin inhibition but also in regulating acute inflammation.
Corbin
L W
LW
Department of Pathology, University of North Carolina School of Medicine, Chapel Hill 27599.
Church
F C
FC
Hoffman
M
M
D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D003871:Dermatan Sulfate / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D015844:Heparin Cofactor II / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors
D011480:Protease Inhibitors; D003871:Dermatan Sulfate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015844:Heparin Cofactor II; D006493:Heparin; D013917:Thrombin